In many diseases and conditions, a favourable outcome of prophylactic and/or therapeutic treatments is strongly correlated with early and/or accurate prediction, diagnosis and/or prognosis of the disease or condition. Therefore, there exists a continuous need for additional and preferably improved manners for early and/or accurate prediction, diagnosis and/or prognosis of diseases and conditions to guide the treatment choices.
Heart failure is a major public health issue in developed countries and is the cause of considerable morbidity and mortality among older adults. It is usually a chronic disease characterised by frequent recurrent decompensation leading to worsening breathing problems. Moreover, 5 years after diagnosis 50% of heart failure patients will have died from the disease.
Acute heart failure (AHF) is a sudden inability of the heart to pump efficiently and where it can no longer foresee the bodily demands for oxygen. AHF is the cause of over two million hospitalisations annually in US and Europe, and displays a mortality rate of about 20-40% within one year of hospital discharge in many populations. About 90% of AHF admissions are typically from patients with chronic heart disease, the remaining about 10% are de novo patients. The clinical signs of heart disease and AHF are often non-specific which can make unambiguous diagnosis demanding.
A common symptom of AHF is the shortness of breath (dyspnea or dyspnoea). However, usually only a fraction of subjects presenting with dyspnea upon admission to a physician or clinic suffer from AHF. Therefore, a rapid, proper and effective treatment of AHF requires to adequately distinguish AHF patients from patients having dyspnea due to other causes.
Currently, diagnosis of AHF is mainly done on the basis of clinical signs, such as, ECG, chest X-ray, etc. One biomarker often used to complement these diagnostic criteria of AHF such as in emergency setting is B-type natriuretic peptide (BNP). Typically, BNP lower than 100 pg/mL is regarded as a “rule-out” criterion for heart failure, whereas BNP higher than 400 pg/mL is seen as a “rule-in” criterion for AHF. Although BNP is sensitive, its specificity is relatively low, and is especially problematic due to the “grey zone” between 100-400 pg/mL. For example, Chung et al. 2006 (Am Heart J 152(5): 949-55) have determined that the BNP cut point of 100 pg/mL has 100% sensitivity but only 41% specificity for diagnosing AHF, whereas the cut point of 400 pg/mL has 87% sensitivity and 76% specificity.
Also, BNP levels vary with age, sex, weight and other medical conditions, thereby confounding the diagnosis. Notably, BNP levels tend to be elevated in patients with medical history of heart failure and renal failure. For example, Chung et al. 2006 (supra) have shown that BNP performance for diagnosing AHF in patients presenting with dyspnea is significantly reduced in patients with a history of heart failure. In particular, about 40% of patients presenting with dyspnea not caused by AHF, who had a history of heart failure, displayed BNP values over 400 pg/mL, the AHF cut-off point used currently in the clinic. Consequently, the European Society of Cardiology (ESC) Guidelines 2008 also characterise BNP as a biomarker of heart failure in general rather than of acute heart failure.
In view of this, there exists a persistent need for additional and preferably specific biomarkers for AHF. Such novel AHF biomarkers may be comparable to or improved over previously existing markers, such as over BNP, in one or more of their characteristics, such as, for example, in their sensitivity and/or specificity, in their reliability in patients presenting with a symptom potentially indicative of AHF such as with dyspnea, in their reliability in patients with history of heart failure and other frequent co-morbidities of heart failure such renal failure, obesity, coronary artery disease etc. WO 2008/037720 e.g. presents a gene expression screening indicating but not verifying that reduced expression of the Quiescin Q6 gene in hearts of the hypertension rat model Ren-2 might be associated with an increased risk of the progression of heart hypertrophy towards congestive heart failure. However, WO 2008/037720 is entirely silent of any utility of Quiescin Q6 polypeptide, and particularly of increased levels thereof, as a biomarker for acute heart failure.
The present invention addresses the above needs in the art by identifying further biomarkers for AHF, and providing uses therefore.